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Age-Specific Epigenetic Drift in Late-Onset Alzheimer's Disease

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Wang, Sun-Chong, Oelze, Beatrice, Schumacher, Axel·2008·PLoS ONE
DOI 10.1371/journal.pone.0002698
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Abstract

Despite an enormous research effort, most cases of late-onset Alzheimer's disease (LOAD) still remain unexplained and the current biomedical science is still a long way from the ultimate goal of revealing clear risk factors that can help in the diagnosis, prevention and treatment of the disease. Current theories about the development of LOAD hinge on the premise that Alzheimer's arises mainly from heritable causes. Yet, the complex, non-Mendelian disease etiology suggests that an epigenetic component could be involved. Using MALDI-TOF mass spectrometry in post-mortem brain samples and lymphocytes, we have performed an analysis of DNA methylation across 12 potential Alzheimer's susceptibility loci. In the LOAD brain samples we identified a notably age-specific epigenetic drift, supporting a potential role of epigenetic effects in the development of the disease. Additionally, we found that some genes that participate in amyloid-beta processing (PSEN1, APOE) and methylation homeostasis (MTHFR, DNMT1) show a significant interindividual epigenetic variability, which may contribute to LOAD predisposition. The APOE gene was found to be of bimodal structure, with a hypomethylated CpG-poor promoter and a fully methylated 3'-CpG-island, that contains the sequences for the epsilon4-haplotype, which is the only undisputed genetic risk factor for LOAD. Aberrant epigenetic control in this CpG-island may contribute to LOAD pathology. We propose that epigenetic drift is likely to be a substantial mechanism predisposing individuals to LOAD and contributing to the course of disease.

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Metadata

Authors
Wang, S.-C., Oelze, B., & Schumacher, A.
Venue
PLoS ONE
Publisher
Public Library of Science (PLoS)
Published
2008-07-16
Volume
3
Issue
7
Pages
e2698
ISSN
1932-6203 (ISSN-L)
DOI
10.1371/journal.pone.0002698
OpenAlex
W2020089910
Cited by
466
References
9
FWCI
11.79
Type
journal article
Language
en
Open access
gold
Licence
creativecommons.org/licenses/by/4.0/ (unspecified)

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CoChat. (2026). Citation check: Age-Specific Epigenetic Drift in Late-Onset Alzheimer's Disease. https://app.cochat.ai/papers/10.1371/journal.pone.0002698
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Wang, S.-C., Oelze, B., & Schumacher, A. (2008). Age-Specific Epigenetic Drift in Late-Onset Alzheimer's Disease. PLoS ONE. https://doi.org/10.1371/journal.pone.0002698

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